Multiple Sclerosis (MS) is also known as disseminated sclerosis and it is one of the world’s most common neurological diseases. It is predominantly defined as formation of plaques in the white matter stemming from damage to the myelin sheaths covering the nerves of the central nervous system (CNS). Ultimately, damage to the myelin sheaths will reduce and block nerve conduction, which may present as a decline in cognitive and motor functions.

 Rumrill Jr., P. (2009). Multiple Sclerosis: Medical and Psychosocial Aspects, Etiology, Incidence, and Prevalence. Journal of Vocational Rehabilitation, 31, 75-82. doi:10.3233/JVR-2009-0476

History of Multiple Sclerosis

1848 – The first reported case of multiple sclerosis. The patient’s name was Augustus D’este, the cousin of Queen Victoria. He died from complications of the disease.

1868 – Multiple sclerosis was defined as a distinct entity by French neurologist and father of neurology, Dr. Jean-Martin Charcot.

1928 – Oligodendrocytes (the cells that make up myelin in the CNS) were discovered. With this discovery, researchers and neurologists could begin to identify the cells that were been destroyed during MS mechanism, as well as begin to theorize a cure for multiple sclerosis.

1935 – Dr. Thomas Rivers introduced the animal model called Experimental Allergic Encephalomyelitis (EAE) model, which will become the go-to model for MS research.

1947 – Dr. Elvin Kabat from Columbia University identified an abnormal immunological protein in the spinal fluid of MS patients. These proteins appeared in patterns, which will be eventually called oligoclonal bands and will serve as a marker for MS during diagnoses.

1946 – Sylvia Lawry fronted the creation of the National MS society in order to promote contacts with neurologists around the world and to raise money to fund research on treatments for Multiple Sclerosis.

1969 – The first valid scientific trial demonstrated findings for a potential steroid therapy for MS symptom management.

1981 – First MRI scan was performed to show the MS plaques and lesions in greater detail that previously used CT scans.

1993 – 2004 – Researchers developed six new drugs that help suppress MS attacks and alter the course of the disease.

Rolak, L.A. (2009). The Basic Facts: The History of MS. Retrieved February 10, 2014, from http://www.nationalmssociety.org/NationalMSSociety/media/MSNationalFiles/Brochures/Brochure-History-of-Multiple-Sclerosis.pdf

Pathophysiology of Multiple Sclerosis

The complete pathogenesis of MS still remains unknown, however, research studies have suggested that there may be certain pathogenetic factors that contribute to tissue injury in the brain. Certain hallmarks of chronic MS include demyelinated plaques, gliosis and astrocystic scars. Some other researchers have suggested that MS is initiated with an increased migration of autoreactive lymphocytes across the blood-brain barrier. The presence of these lymphocytes in the blood brain barrier may become pathologic as a result of regulatory defects that activate these lymphocytes to mediate an immune response within the brain. On a cellular level, these regulatory lymphocytes in MS patients fail to suppress effector cells from being autoreactive. This in turn leads to the over expression of β-arrestin 1, which is a promoter of naive and activated CD4+ T-cell survival. Thus, a cascade of events due to the failure of the regulatory mechanisms within the brain accounts for distinct sites of inflammation, dominated by perivascular CD8+ cell infiltration, which cause the characteristic MS plaques. These plaques are often found in cluster formations around primary sites of damage such as lateral ventricles, corpus callosum and subcortical white matter, as well as the optic nerves, brainstem and throughout the spinal cord. Other studies have aimed to determine the primary lymphocytic culprit permeating the blood-brain barrier. The T-lymphocyte subtype is frequently suggested since it has been found to initiate inflammation by also secreting interleukin-17 and 22. These factors eventually disrupt the human blood-brain barrier by allowing the efficient penetration of another factor, T-helper 17 cells, into the brain to kill human neurons.

Alastair, C., & Alastair C. (2008). Multiple Sclerosis. The Lancet, 372, 1502-1517.
Noseworthy, J.H., Lucchinetti, C., Rodriguez, M., & Weinshenker, B.G. (2000). MultipleSclerosis. The New England Journal of Medicine, 343(13), 938-952.

Symptoms of Multiple Sclerosis

MS symptoms typically vary from person to person, since the symptoms that an MS patient experience are contingent on the location and size of plaques in the CNS. Initial symptoms of MS may include weakness or diminished dexterity in one or more limbs, sensory disturbances, optic neuritic visual loss, gait instability, and ataxia. As the disease worsens, bladder dysfunction, MS fatigue, and heat sensitivity known as Uthoff’s phenomena, occurs in most patients. Other symptoms include Lhermitte’s syndrome, which is an electric shock-like sensation down the spine and into the limbs evoked by neck flexion, hemifacial weakness or pain, useless hand syndrome, vertigo, and other paroxysmal symptoms. Cognitive deficits are also common, especially in advanced cases, which include memory loss, impaired attention, problem-solving difficulties, slowed information processing, and difficulties in shifting between cognitive tasks.

Multiple Sclerosis Society of Canada. (2014a). About MS: Managing MS Symptoms. Retrieved February 10, 2014, from http://mssociety.ca/en/information/symptoms.htm

Types of Multiple Sclerosis

There are four major courses that are used to classify MS.

  • Relapse-Remitting: This is the predominant form affecting almost 80% of MS patients with a female to male ratio of 2:1 at the time of diagnosis. It is typically characterized by visible attacks of symptoms, or relapses, lasting from days to weeks, which may be followed by partial or incomplete recovery periods, termed remissions.
  • Primary Progressive: It is characterized as a slow and steady decline in motor functioning from the onset of the disease without any noticeable periods of recovery. This form commonly occurs in MS patients diagnosed after age 40, and accounts for about 10% of MS cases.
  • Secondary Progressive: It is characterized as relapse-remitting MS that eventually develops into a steady progressive course, with or without remissions. It has been estimated that two-thirds of those diagnosed with the relapse-remitting variant of MS eventually develop the secondary progressive form.
  • Progressive Relapsing: This is the rarest course of MS, occurring in only about 5% of cases. It is defined as a steady and progressive course of declining function over time, accompanied by periods of clear and significant relapses, where symptoms worsen without warning.
Noseworthy, J.H., Lucchinetti, C., Rodriguez, M., & Weinshenker, B.G. (2000). MultipleSclerosis. The New England Journal of Medicine, 343(13), 938-952.
Rumrill Jr., P. (2009). Multiple Sclerosis: Medical and Psychosocial Aspects, Etiology, Incidence, and Prevalence. Journal of Vocational Rehabilitation, 31, 75-82. doi:10.3233/JVR-2009-0476

Diagnosis & Treatment Of Multiple Sclerosis

The current standard criterion used to diagnose MS is called the McDonald criteria. It is used to objectively measure the dissemination of lesions based on one or more of the three major tests used in successfully diagnosing MS. These tests may include neuroimaging scans that are used to visualize the areas of lesions and plaques in the CNS, spinal tap helps provide evidence of CNS inflammation by the presence of oligoclonal IgG bands detected in the cerebrospinal fluid proteins, as well as evoked potentials, which is a test used to measure the speed of nerve impulse conduction in the CNS pathways.

There has been no known cure developed for MS, therefore, the treatment process focuses on symptom management, as well as strategies for maintaining a good mental health status. The ultimate goal is to maximize functioning and overall quality of life. Currently, some steroid medications are used to actively suppress inflammation specifically in cases of the relapse-remitting course of MS, and some other drugs that have been used in symptom management include MS disease-modifying drugs, Novantrone and Cyclosporin, as well as beta-inferons, Avonex and Betaseron. These treatment options are effective ways for targeting the different courses of MS, however none of these treatments offer a curative approach to the disease.

Multiple Sclerosis Society of Canada. (2014b). About MS: Diagnosing Multiple Sclerosis. Retrieved February 10, 2014, from http://mssociety.ca/en/information/ms_diagnose.htm
Multiple Sclerosis Society of Canada. (2014c). About MS: Types and Treatment. Retrieved February 10, 2014, from http://mssociety.ca/en/information/ms_typetreat.htm
Multiple Sclerosis Neuroimaging Scan
Multiple Sclerosis Neuroimaging Scan

Co-Morbidities Of Multiple Sclerosis

The co-morbidities of MS are not well developed, however MS has been linked to several mental health issues such as depression and anxiety, bipolar disorder, and diurnal mood change. In addition, there are also autoimmune co-morbid issues that have been associated with MS and they include Hashimoto’s thyroiditis, inflammatory bowel disease, hypertension, arthritis and psoriasis.

Berkovich, R., Dagwood, S., Steinman, L. (2011). Autoimmune comorbid conditions in Multiple Sclerosis. US Neurology, 7(2), 132-138
Marie, R. A., Hanwell, H. (2013). General health issues in multiple sclerosis: Comorbidities, secondary conditions, and health behaviors. Continuum, 19(4), 1046-1057.

Epidemiology Of Multiple Sclerosis

A North-South gradient has been described for MS, suggesting that it is particularly more common in temperate zones of the northern and southern hemispheres, as well as areas further from the equator. Some explanations of this zone and region specificity include differences in genetics, as well as nature and nurture interactions. An exposure to sunlight and its effect on the association between MS and Vitamin D levels has been postulated to be an explanation for this specific distribution of MS. Nonetheless, prevalence of MS continues to be higher in the said areas further from the equator, such as regions of Europe, Canada, the United States and Australia. Furthermore, in 2013, the World Health Organization (WHO) found that almost 2.3 million people worldwide were living with MS. In Canada specifically, the prevalence rate is 291 per 100,000 persons with approximately 4,550 new incidences of MS appearing each year. Fewer rates of MS have been found in populations of Hispanic, Asian and African descent, with prevalence rates occurring in the low range of 0-60 per 100,000 persons. Countries in North America and Europe have prevalence rates up to 3-4 times higher than those of Africa and Asia.

Like other autoimmune disorders, MS affects more women than men, with the female to male ratio being almost 3 to 1 in high prevalent countries. In addition, MS Symptoms tend to appear between the ages of 30-35 years, and clinical diagnosis generally occurs between 20-50 years of age.

Atlas of MS. (2013). Mapping Multiple Sclerosis Around The World. Multiple Sclerosis International Federation. Retrieved from http://www.atlasofms.org/
Beck, C. A., Metz, L.M., Svenson, L. W. Patten, S. B. (2005). Regional variation of multiple sclerosis prevalence in Canada. Multiple Sclerosis Journal, 11(5), 516-519.
Koch-Henriksen, N., & Sorensen, P. S. (2011). Why does the north–south gradient of incidence of multiple sclerosis seem to have disappeared on the northern hemisphere? Journal of the Neurological Sciences, 311(1), 58-63.

Causes & Risk factors Of Multiple Sclerosis

There is no known linear cause of MS, however, extensive evidence show the roles that genetic, viral and vitamin deficiency play in the acquisition of MS. In 1973, it was recognized that MS is strongly associated with the human leukocyte antigen region. Specifically, familial studies demonstrate that the HLA-DR2 homozygous allele renders an individual susceptible to MS, but the magnitude of risk increase that results from the presence of this allele has not yet been identified. Other risk factors associated with MS are Vitamin D deficiency and exposure to the Epstein-Barr virus (EBV). Vitamin D levels and MS are inversely related with higher levels of vitamin D serving as a protective factor for the risk of developing MS. Studies focusing on the viral association show that most individuals with MS have also been previously infected with EBV, and high levels of the EBV antibody increase the risk of developing MS in those who do not already have the disease.

Jersild, C., Fog, T., Hansen, G. S., Thomsen, M., Svejgaard, A., Dupont, B. (1973). Histocompatibility determinants in Multiple Sclerosis, with special reference to clinical course. Lancet, 2(7840), 1221-1225.
Levin, L. I., Munger, K. L., Hollis, B. W. V., Howard, N. S., Ascherio, A., Levin, L. I., et al. (2006). Serum 25- hydroxyvitamin D levels and risk of multiple sclerosis. JAMA, the Journal of the American Medical Association, 296(23), 2832.

The Psychosocial Impact Of Multiple Sclerosis

The effects of MS are not restricted to the diagnosed individual, but filtrate into proximate interpersonal relationships. Many individuals report benefits such as improved communication and closeness within their family, as well as appreciation for life and compassion towards others.

The subjective experience is often described in terms of the effects on family and friends, specifically the individual who assumes the caregiver role. While some relationships find profound benefits, others may succumb to the stresses, and deteriorate. Adaptation to illness and its consequences can be difficult for all of those involved. As the age bracket most commonly impacted is young adults and adults, romantic relationships and marriages experience some of the greatest challenges.

It is also important to recognize the potential for MS to impact the educational aspect of a young adult’s life. Variable symptoms and relapses, as well as physical disability may impede a young student’s consistency in academic attendance. This combined with the possible cognitive delays, may greatly restrict the possibilities for learning and education. Thus, the close link between education, employment and socioeconomic status means that cognitive delays that prevent MS patients from furthering their knowledge and pursuing higher educations may impede career-related prospects later in life.

MS patients are also often faced with disease-related stigma. As with all diseases associated with debilitation, some patients with MS report feeling stigmatized, especially by society. Although this disease is not always visibly recognizable, symptoms such as fatigue, slowed speech and information processing, as well as reduced memory attention may be misperceived. Individuals unaware of the course and appearance of MS, may presume that MS patients are unmotivated and lazy, or unintelligent based on MS symptom presentations.

Multiple Sclerosis Society of Canada. (2014a). About MS: Managing MS Symptoms. Retrieved February 10, 2014, from http://mssociety.ca/en/information/symptoms.htm

Recent Research & Findings on Multiple Sclerosis

Some studies have shown that with increasing age, stem cells (that typically regenerate cells including oligodendrocytes, which have been presumed to be directly involved with MS etiology) in the brain become less efficient. Recent findings have also analyzed other functions of microRNAs. These are small non-coding RNAs that are of great importance because of their ability to reprogram stem cell self-renewal, which will be greatly beneficial in less severe cases of MS. Essentially, a reprogramming or renewal of stem cells by microRNAs will ensure that oligodendritic cell damage and repair are occurring at the same rate, such that as oligodendrocytes are being destroyed in the CNS of an MS patient, stem cells differentiate and activate to produce more oligodendrocytes that will counter and replace the damaged ones. Thus, the relationship between microRNAs and stem cells may prove beneficial in designing drug and gene therapies for curing MS.

Other studies have begun to analyze the effectiveness of cognitive reserves as a protective factor for MS. Since MS may progress to cause cognitive impairments, these studies suggest that severe cognitive defects may be controlled for by high cognitive reserves. High cognitive reserves are typically achieved from a heritable maximal lifetime brain growth, and environmental factors including greater knowledge & education, increased participation in cognitive leisure activities (e.g. reading, hobbies) and a greater social interaction. The idea is that high cognitive reserves decrease the portrayal of cognitive impairments in MS patients despite the occurrence of pathologic factors such as white matter lesions, cerebral atrophy and plaque formation. The complete biological mechanism and protective factor of cognitive reserve on MS is still being studied but this may lead future research into determining certain behavioral therapies for MS symptoms.

Gangaraju, V.K., & Lin, H. (2009). MicroRNAs: Key Regulators of Stem Cells. Nature Reviews Molecular Cell Biology, 10, 116-125. doi: 10.1038/nrm2621
Hybertsen, S. (Director). (2013). Multiple Sclerosis, The Vikings and Nordic Skiing [Documentary]. United States.
Sumowski, J. F. & Leavitt, V. M. (2013). Cognitive Reserve In Multiple Sclerosis. Multiple Sclerosis Journal, 19 (9), 1122-1127. doi: 10.1177/1352458513498834

Note: This research article on Multiple Sclerosis is a combined effort of two University graduates, Zainab & Morgan. In their final year of University, they acquired a curiosity on the inception and progression of Multiple Sclerosis, a formidable entity in the society. They aimed to research and amalgamate the current knowledge that is known about Multiple Sclerosis. After three months and some sleepless nights, they successfully combined what seemed to be an imperfect journey of Multiple Sclerosis from its history to what is being done to reduce its severity. For those curious and willing to find a successful pop culture depiction of Multiple Sclerosis, and a film that Zainab and Morgan used extensively as a major reference for this article, watch the film titled, “Duet For One”, which stars our favourite Maria Von Trapp…Miss Julie Andrews.

*The italicized sentences present below each subcategory represent the references used for that section.